Passively inhaled tobacco smoke: a challenge to toxicology and preventive medicine

Publisher Website
Google Scholar
Abstract
The difficulties in defining the exposure of a passive smoker might explain the controversial results regarding an association between passive smoking on one hand and lung cancer, tumors of all sites and ischemic heart diseases on the other. The plausibility of these epidemiological observations will be discussed in the light of analytical, toxicological, biochemical and oncological data. The minute amounts of nicotine and particulate matter, even the much higher concentrations of volatile substances, such as nitrosamines, NOx, acroleine and formaldehyde, present in diluted sidestream compared to mainstream smoke and breathed by involuntarily smoking people, cannot explain their relatively high cancer risk. It is plausible if one considers the high capacity of cigarette smoke to induce drug metabolizing enzymes. Diluted sidestream smoke, however,lacks compounds which induce several iso-enzymes of cyt. P-450 monooxygenase in the tissues. The best evidence is the up to 100-fold increase in placental enzymes if pregnant women smoke, whereas passively inhaled tobacco smoke is ineffective as inducer. The small amounts of paternal smoke inhaled by pregnant women, containing teratogenic and carcinogenic compounds, which are supposedly not detoxified in the placenta, seem to explain the higher risk for malformations of the fetus and the same or even increased risk for perinatal mortality, compared with the outcome of pregnancy if the mother smoked. The induction of placental enzymes very probably protects the fetus against the much higher amounts of toxic agents inhaled by the smoking mother. The increased activity of placental enzymes seems to be a model for the probably greater capacity of certain cyt. P-450 iso-enzymes in the lung and other tissues to convert carcinogens to inactive metabolites when the individual smokes actively. It is well known that concomitant administration of carcinogens with inducing agents inhibits tumor growth in animals because of a shift in the metabolism which favours the formation of ineffective substances. The negligible amounts of nicotine and CO in passively inhaled tobacco smoke cannot be responsible for the surprisingly high risk for ischemic heart diseases of passive smokers. A plausible explanation is offered by experiments with doves and chicken, which develop atherosclerotic lesions due to the action of carcinogens which are metabolized by certain inducible cyt. P-450 iso-enzymes in the aortic wall. Much circumstantial evidence will be presented, indicating that PAHs, contrary to the propagated opinion, play a minor role for the initiation of cancer in active smokers. Tobacco specific nitrosamines and pyrolysis products have to be considered more seriously. Enzyme induction in the tissues of active smokers is very probably the most important confounding factor which explains the approaching health risks of active and passive smokers.